Purpose:
ONO-0476 is potent and selective prostanoid EP2 receptor agonist manufactured by ONO Pharmaceutical Co., Ltd. The purpose of this study is to evaluate IOP-lowering effects of concomitant use of ONO-0476 and existing drugs (timolol or latanoprost) in normotensive cynomolgus monkeys.

Methods:
Male cynomolgus monkeys received 7-day repeated topical dosing as follows: (1; ONO group) ONO-0476 (0.3 μg/mL) and vehicle in the morning (AM) and vehicle in the evening (PM), (2; ONO+TIM group) ONO-0476 and timolol (5 mg/mL) in AM and timolol in PM, (3; ONO+LAT group) ONO-0476 and latanoprost (50 μg/mL) in AM and vehicle in PM. All dosing were performed at a volume of 30 μL. IOP was evaluated by using applanation pneumatonometer just before AM dosing on day 0, and at 4, 8, 12, 24,and 48 hours after AM dosing on day 7.

Results:
ONO-0476 showed potent reduction of IOP (maximal reduction of IOP in ONO group: 6.9±0.4 mmHg, n=3), and this effect is long lasting (reduction of IOP at 24 hour on day 7: 5.0±0.4 mmHg, n=3). Furthermore, concomitant use of ONO-0476 and existing drugs showed more reduction of IOP than the sole use of ONO-0476 (maximal reduction of IOP in ONO+TIM group: 7.4±0.1 mmHg, n=3, in ONO+LAT group: 8.6±0.4 mmHg, n=3).

Conclusions:
ONO-0476 could provide a new and an attractive option for glaucoma therapy both as initial treatment of single use and as stepwise treatment of combination drug with other existing drugs.